The many striking clinical responses reported in recent years after treatment of cancer patients with tumor vaccines bares testimony to the potential for this approach. To establish a firmer foundation for future clinical trials it will be necessary to take a stepwise approach based on a knowledge of the antigens expressed by tumors, the immune response induced against these antigens by vaccination and approaches available for augmenting vaccine immunogenicity. Recent technological advances have revolutionized this approach. This conference will begin with a review of the 3 foundations for therapy of cancer with vaccines: 1) preclinical studies with tumor vaccines; 2) progress in infectious disease vaccines; and 3) experimental autoimmunity. Immune mechanisms relevant to vaccine effectiveness including antigen processing, presentation and recognition, effector mechanisms of tissue destruction, and the mechanisms for escape from immune destruction will be reviewed. Tumor antigens relevant for vaccine construction will be described and the results of recent clinical trials with tumor vaccines will be presented. This will be followed by a discussion of the mechanisms for further augmented the immunogenicity of 1) purified tumor antigens including the newer adjuvants, immunomodulators, and conjugate vaccines involving carrier protein or viral or bacterial vectors, and 2) whole tumor cells including cytokine gene transfection, mutagenization and xenogenization. The session will close with the NCI perspective on therapy of cancer with vaccines. Technological advances in the related fields of basic immunology and infectious disease vaccinology effect all aspects of tumor vaccine development and offer enormous promise for the therapy of cancer with vaccines, making this conference both timely and necessary.